Integrated Chromosome 19 Transcriptomic and Proteomic Data Sets Derived from Glioma Cancer Stem-Cell Lines

Abstract

One subproject within the global Chromosome 19 Consortium is to define chromosome 19 gene and protein expression in glioma-derived cancer stem cells (GSCs). Chromosome 19 is notoriously linked to glioma by 1p/19q codeletions, and clinical tests are established to detect that specific aberration. GSCs are tumor-initiating cells and are hypothesized to provide a repository of cells in tumors that can self-replicate and be refractory to radiation and chemotherapeutic agents developed for the treatment of tumors. In this pilot study, we performed RNA-Seq, label-free quantitative protein measurements in six GSC lines, and targeted transcriptomic analysis using a chromosome 19-specific microarray in an additional six GSC lines. The data have been deposited to the ProteomeXchange with identifier PXD000563. Here we present insights into differences in GSC gene and protein expression, including the identification of proteins listed as having no or low evidence at the protein level in the Human Protein Atlas, as correlated to chromosome 19 and GSC subtype. Furthermore, the upregulation of proteins downstream of adenovirus-associated viral integration site 1 (AAVS1) in GSC11 in response to oncolytic adenovirus treatment was demonstrated. Taken together, our results may indicate new roles for chromosome 19, beyond the 1p/19q codeletion, in the future of personalized medicine for glioma patients.

Association of chromosome 19 to lung cancer genotypes and phenotypes

“…The Chromosome 19 Consortium has investigated gene expression using complementary analysis platforms, to provide a genomewide human protein resource database, and detailed maps of protein molecular pathways, interactions, and networks. The Chromosome 19 project has already contributed to the annotations of severe diseases, especially glioblastoma [11][12][13].…”

Quantitative proteomics and transcriptomics reveals metabolic differences in attracting and non-attracting human-in-mouse glioma stem cell xenografts and stromal cells

“…However, GSCXs exhibiting differential attraction of for BM-hMSCs have not been systematically studied at either the proteomic or transcriptomic level. We utilized label-free quantitative proteomics as a reliable technique previously employed by our lab [23,50] that is cost effective, yields high proteome coverage, and does not suffer from dynamic range limitations [37,51]. We also utilized a targeted transcriptomic platform [45][46][47], which contains genesets related to GBM biology, in parallel to label-free proteomics (Fig.…”

“…Chromatographic separations were performed with a nano-LC chromatography system (Easy-nLC 1000, Thermo Scientific) For each sample, the five most abundant precursor ions above a 10,000 count threshold were selected from each survey scan (MS) for HCD fragmentation (isolation width AE2.0 Da, default charge state of 4, normalized collision energy 30%, activation Q 0.250, and activation time 0.1 s as previously described [23,30]). Ion injection times for the MS and MS/MS scans were 500 ms each.…”

“…PEAKS automatically generated a decoyfusion, which appended a decoy sequence to each protein for calculation of FDR [32]. All modifications in the Unimod database were considered in the PEAKS search [23,33]. PEAKS searches were performed with a precursor ion mass tolerance of 10 ppm and fragment mass tolerance was 0.1 Da.…”

“…Therefore, we hypothesized that alteration of the proteomic profile of cancer and stromal cell populations between attractor and non-attractor GSC xenografts may provide insights into key biochemical pathways involved in the attraction of BM-hMSCs to gliomas. We have previously performed label-free quantitative proteomic and targeted transcriptomic studies on GSCs and GBM cells [23][24][25][26]. For the first time, we extend these methodologies to attractor and non-attractor GSCXs.…”